The ability of macrophages to destroy foreign cells such as bacteria and neoplastic cells forms the basis of an important mechanism of host defense. Although macrophage cytocidal activity appears to be a composite of three reactions involving activation, recognition and target cell killing, detailed information of the mechanisms involved in these processes has remained scarce. This research seeks to elucidate the molecular events which lead to macrophage activation and to determine the effect of activation on macrophage recognition reactions and effector cell function. This past year, particular emphasis was placed on the purification and characterization of the soluble T-lymphocyte product, denoted macrophage activating factor (MAF), which is responsible for inducing macrophage cytocidal activity. On the basis of a variety of biosynthetic, physiochemical and immunochemical criteria we have found that the MAF activity, produced by a murine T-cell hybridoma is totally attributable to gamma interferon. Using partially purified or purified MAF preparations, the mechanism of action of this lymphokine will be determined. Because of the recent reports that certain complement proteins can mimic specific lymphokines and influence activation of mononuclear phagocytes, the role of complement in the induction of macrophage cytocidal activity also will be examined. The membrane structures on macrophages which recognize target cells will be characterized. Phagocyte complement receptors also will be defined. A detailed analysis will be performed to quantitate the effects of activation on the function of these two types of cellular recognition structures. The results of these studies should provide additional insights into the molecular basis of macrophage function and thus enhance our understanding of the host defense system.